The human interleukin-2 receptor is being studied to understand critical components of the T cell immune response in normal and neoplastic cells. When T-cells are activated by antigen or mitogenic lectin, both IL-2 and IL-2 receptor expression are induced. IL-2 and IL-2 receptors control the magnitude and duration of the T-cell immune response based on the amount of IL-2 produced, the levels of receptors expressed, and the time course of each of these events. Whereas low levels of intermediate affinity IL-2 receptors are expressed on resting cells, following antigen stimulation expression of both high and low affinity IL-2 receptors is potently induced. Three chains of the IL-2 receptor are now known to exist, namely IL-2Ralpha, IL-2Rbeta, and IL-2Rgamma. Dr. Leonard cloned IL-2Ralpha as a post-doctoral fellow, and the current lab discovered IL- 2Rbeta. In the past year, major advances have been made in a number of areas. Significant progress has been made in studies utilizing the expression of the IL-2Ralpha and beta chain cDNAs in 32D cells (a system developed by this lab) to elucidate features of IL-2 mediated signal transduction. This system has now allowed the demonstration that tyrosine kinases can regulate bcl-2 and apoptosis, and that tyrosine kinase inhibitors can induce apoptosis. Multiple IL-2Rbeta mutants for use in signaling studies have been prepared. It has also been demonstrated for the first time that human neutrophils express IL-2 receptors and respond to IL-2. Their response allows cytotoxicity towards tumor targets and the killing of Candida albicans, a fungus which can cause human disease. Furthermore and most significantly, the laboratory has determined that mutation of the IL-2Rgamma chain results in X-linked severe combined immunodeficiency (XSCID) in humans. This finding has profound fundamental implications in T-cell immunology as well as clinical medicine.